Sumoylation is an evolutionarily conserved regulatory mechanism to play an important role in various cellular processes through modulation of protein localization, stability and functionality. Recent studies including ours have consistently demonstrated that sumoylation provides protection for cells against oxidative stress. Given that pancreatic beta cells are a vulnerable target of oxidative stress, we thus in this minireview, updated the advancement of sumoylation in the regulation of ROS generation, and discussed its impact on several critical signaling pathways relevant to beta cells against oxidative stress and maintenance of functionality. Specifically, we bring together how sumoylation represses intracellular ROS formation, and protects beta cells against oxidative stress through regulating I kappa B/NF kappa B, JNK/c-Jun, and Maf/Nrf2 pathways. The tight implication of sumoylation in oxidative stress reflects that it could be an essential mechanism for beta cells to adapt to the detrimental cellular microenvironment.